{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:07:31Z","timestamp":1791925651469,"version":"4.3.4"},"reference-count":99,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T00:00:00Z","timestamp":1633737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Geistlich Pharma (Switzerland)","award":["300409-101"],"award-info":[{"award-number":["300409-101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Aim: To immunohistochemically evaluate the effect of a volume-stable collagen scaffold (VCMX) on periodontal regeneration. (2) Methods: In eight beagle dogs, acute two-wall intrabony defects were treated with open flap debridement either with VCMX (test) or without (control). After 12 weeks, eight defects out of four animals were processed for paraffin histology and immunohistochemistry. (3) Results: All defects (four test + four control) revealed periodontal regeneration with cementum and bone formation. VCMX remnants were integrated in bone, periodontal ligament (PDL), and cementum. No differences in immunohistochemical labeling patterns were observed between test and control sites. New bone and cementum were labeled for bone sialoprotein, while the regenerated PDL was labeled for periostin and collagen type 1. Cytokeratin-positive epithelial cell rests of Malassez were detected in 50% of the defects. The regenerated PDL demonstrated a larger blood vessel area at the test (14.48% \u00b1 3.52%) than at control sites (8.04% \u00b1 1.85%, p = 0.0007). The number of blood vessels was higher in the regenerated PDL (test + control) compared to the pristine one (p = 0.012). The cell proliferative index was not statistically significantly different in pristine and regenerated PDL. (4) Conclusions: The data suggest a positive effect of VCMX on angiogenesis and an equally high cell turnover in the regenerated and pristine PDL. This VCMX supported periodontal regeneration in intrabony defects.<\/jats:p>","DOI":"10.3390\/ijms222010915","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T21:23:25Z","timestamp":1633901005000},"page":"10915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Immunohistochemical Evaluation of Periodontal Regeneration Using a Porous Collagen Scaffold"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-5249","authenticated-orcid":false,"given":"Jean-Claude","family":"Imber","sequence":"first","affiliation":[{"name":"Department of Periodontology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland"},{"name":"Robert K. Schenk Laboratory of Oral Histology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-0860","authenticated-orcid":false,"given":"Andrea","family":"Roccuzzo","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"St\u00e4hli","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3960-4920","authenticated-orcid":false,"given":"Nikola","family":"Saulacic","sequence":"additional","affiliation":[{"name":"Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, Faculty of Medicine, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Deschner","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University Medical Centre of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-5477","authenticated-orcid":false,"given":"Anton","family":"Sculean","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter Daniel","family":"Bosshardt","sequence":"additional","affiliation":[{"name":"Department of Periodontology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland"},{"name":"Robert K. Schenk Laboratory of Oral Histology, School of Dental Medicine, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1902\/jop.2015.140379","article-title":"Periodontal regeneration\u2014Furcation defects: A systematic review from the AAP Regeneration Workshop","volume":"86","author":"Reddy","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/prd.12048","article-title":"Clinical concepts for regenerative therapy in intrabony defects","volume":"68","author":"Cortellini","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1902\/jop.2015.130685","article-title":"Periodontal regeneration\u2014Intrabony defects: A systematic review from the AAP Regeneration Workshop","volume":"86","author":"Kao","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1111\/jcpe.12546","article-title":"Twenty years of enamel matrix derivative: The past, the present and the future","volume":"43","author":"Miron","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1902\/jop.2015.140378","article-title":"Periodontal regeneration\u2014Intrabony defects: A consensus report from the AAP Regeneration Workshop","volume":"86","author":"Reynolds","year":"2015","journal-title":"J. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/prd.12081","article-title":"Clinical concepts for regenerative therapy in furcations","volume":"68","author":"Sanz","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/prd.12086","article-title":"Biomaterials for promoting periodontal regeneration in human intrabony defects: A systematic review","volume":"68","author":"Sculean","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1600-0765.2012.01478.x","article-title":"Growth and differentiation factors for periodontal regeneration: A review on factors with clinical testing","volume":"47","author":"Stavropoulos","year":"2012","journal-title":"J. Periodontal Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/prd.12362","article-title":"Microbial signatures of health, gingivitis, and periodontitis","volume":"86","author":"Abusleme","year":"2021","journal-title":"Periodontol. 2000"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/prd.12296","article-title":"The role of the microbiota in periodontal disease","volume":"83","author":"Curtis","year":"2020","journal-title":"Periodontol. 2000"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/prd.12377","article-title":"Microbial transitions from health to disease","volume":"86","author":"Joseph","year":"2021","journal-title":"Periodontol. 2000"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/jcpe.12643","article-title":"Regenerative potential of leucocyte- and platelet-rich fibrin. Part A: Intra-bony defects, furcation defects and periodontal plastic surgery. A systematic review and meta-analysis","volume":"44","author":"Castro","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1600-051X.2008.01263.x","article-title":"Regeneration of periodontal tissues: Combinations of barrier membranes and grafting materials\u2014Biological foundation and preclinical evidence: A systematic review","volume":"35","author":"Sculean","year":"2008","journal-title":"J. Clin. Periodontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/prd.12057","article-title":"Wound healing following surgical and regenerative periodontal therapy","volume":"68","author":"Susin","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Caball\u00e9-Serrano, J., Zhang, S., Ferrantino, L., Simion, M., Chappuis, V., and Bosshardt, D.D. (2019). Tissue Response to a Porous Collagen Matrix Used for Soft Tissue Augmentation. Materials, 12.","DOI":"10.3390\/ma12223721"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S1369-7021(11)70058-X","article-title":"Biomaterials & scaffolds for tissue engineering","volume":"14","year":"2011","journal-title":"Mater. Today"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sbricoli, L., Guazzo, R., Annunziata, M., Gobbato, L., Bressan, E., and Nastri, L. (2020). Selection of Collagen Membranes for Bone Regeneration: A Literature Review. Materials, 13.","DOI":"10.3390\/ma13030786"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rico-Llanos, G.A., Borrego-Gonz\u00e1lez, S., Moncayo-Donoso, M., Becerra, J., and Visser, R. (2021). Collagen Type I Biomaterials as Scaffolds for Bone Tissue Engineering. Polymers, 13.","DOI":"10.3390\/polym13040599"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S123","DOI":"10.1111\/jcpe.12185","article-title":"The addition of soft tissue replacement grafts in plastic periodontal and implant surgery: Critical elements in design and execution","volume":"41","author":"Zuhr","year":"2014","journal-title":"J. Clin. Periodontol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/JPER.19-0351","article-title":"Extracellular matrix-based scaffolding technologies for periodontal and peri-implant soft tissue regeneration","volume":"91","author":"Tavelli","year":"2020","journal-title":"J. Periodontol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Caball\u00e9-Serrano, J., Zhang, S., Sculean, A., Staehli, A., and Bosshardt, D.D. (2020). Tissue Integration and Degradation of a Porous Collagen-Based Scaffold Used for Soft Tissue Augmentation. Materials, 13.","DOI":"10.3390\/ma13102420"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1600-051X.2010.01581.x","article-title":"Soft tissue volume augmentation by the use of collagen-based matrices: A volumetric analysis","volume":"37","author":"Thoma","year":"2010","journal-title":"J. Clin. Periodontol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/jcpe.12588","article-title":"Randomized controlled clinical study evaluating effectiveness and safety of a volume-stable collagen matrix compared to autogenous connective tissue grafts for soft tissue augmentation at implant sites","volume":"43","author":"Thoma","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/jcpe.12697","article-title":"Randomized controlled clinical study comparing a volume-stable collagen matrix to autogenous connective tissue grafts for soft tissue augmentation at implant sites: Linear volumetric soft tissue changes up to 3 months","volume":"44","author":"Zeltner","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1002\/bit.22893","article-title":"A bioreactor test system to mimic the biological and mechanical environment of oral soft tissues and to evaluate substitutes for connective tissue grafts","volume":"107","author":"Mathes","year":"2010","journal-title":"Biotechnol. Bioeng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1600-051X.2011.01794.x","article-title":"The proteome and gene expression profile of cementoblastic cells treated by bone morphogenetic protein-7 in vitro","volume":"39","author":"Bozic","year":"2012","journal-title":"J. Clin. Periodontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.bone.2017.08.027","article-title":"Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis","volume":"105","author":"Ao","year":"2017","journal-title":"Bone"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/0022034512469026","article-title":"Deficiency in acellular cementum and periodontal attachment in bsp null mice","volume":"92","author":"Foster","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S8756-3282(01)00573-7","article-title":"Expression of cementum-derived attachment protein in bovine tooth germ during cementogenesis","volume":"29","author":"Saito","year":"2001","journal-title":"Bone"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1096\/fasebj.6.11.1644261","article-title":"Production of a monoclonal antibody to an attachment protein derived from human cementum","volume":"6","author":"Arzate","year":"1992","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1177\/00220345000790070901","article-title":"Cementum attachment protein enriches putative cementoblastic populations on root surfaces in vitro","volume":"79","author":"BarKana","year":"2000","journal-title":"J. Dent. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1002\/jbmr.5650110517","article-title":"Characterization of a collagenous cementum-derived attachment protein","volume":"11","author":"Wu","year":"1996","journal-title":"J. Bone Min. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1359\/jbmr.1999.14.7.1239","article-title":"Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta","volume":"14","author":"Horiuchi","year":"1999","journal-title":"J. Bone Min. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/dvdy.10453","article-title":"Periostin is expressed within the developing teeth at the sites of epithelial-mesenchymal interaction","volume":"229","author":"Wang","year":"2004","journal-title":"Dev. Dyn"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00441-002-0664-2","article-title":"The divergent expression of periostin mRNA in the periodontal ligament during experimental tooth movement","volume":"312","author":"Wilde","year":"2003","journal-title":"Cell Tissue Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1083\/jcb.200603161","article-title":"New consensus nomenclature for mammalian keratins","volume":"174","author":"Schweizer","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00418-008-0435-6","article-title":"The human keratins: Biology and pathology","volume":"129","author":"Moll","year":"2008","journal-title":"Histochem Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.clinbiochem.2004.05.009","article-title":"Clinical utility of cytokeratins as tumor markers","volume":"37","author":"Barak","year":"2004","journal-title":"Clin. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"127","DOI":"10.5005\/jp-journals-10024-1502","article-title":"Oral cytokeratins in health and disease","volume":"15","author":"Rao","year":"2014","journal-title":"J. Contemp Dent. Pract."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1034\/j.1600-0765.2001.036004260.x","article-title":"Patterns of cytokeratin expression in monkey and human periodontium following regenerative and conventional periodontal surgery","volume":"36","author":"Sculean","year":"2001","journal-title":"J. Periodontal Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/clr.12543","article-title":"Cell-to-cell communication--periodontal regeneration","volume":"26","author":"Bosshardt","year":"2015","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/prd.12023","article-title":"Role of the epithelial cell rests of Malassez in the development, maintenance and regeneration of periodontal ligament tissues","volume":"63","author":"Xiong","year":"2013","journal-title":"Periodontol. 2000"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1034\/j.1600-0765.2003.01636.x","article-title":"Immunohistochemical characteristics of epithelial cell rests of Malassez during cementum repair","volume":"38","author":"Hasegawa","year":"2003","journal-title":"J. Periodontal Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/j.1600-051X.1996.tb01821.x","article-title":"The periodontal tissues in healed degree III furcation defects. An experimental study in dogs","volume":"23","author":"Berglundh","year":"1996","journal-title":"J. Clin. Periodontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1600-0765.1998.tb02204.x","article-title":"Absence of Malassez epithelial rests in the regenerated periodontal ligament. A pilot study in the monkey","volume":"33","author":"Sculean","year":"1998","journal-title":"J. Periodontal Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/(SICI)1097-0185(199801)250:1<13::AID-AR3>3.0.CO;2-F","article-title":"Developmental appearance and distribution of bone sialoprotein and osteopontin in human and rat cementum","volume":"250","author":"Bosshardt","year":"1998","journal-title":"Anat. Rec."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/ijos.2012.57","article-title":"Methods for studying tooth root cementum by light microscopy","volume":"4","author":"Foster","year":"2012","journal-title":"Int. J. Oral Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1902\/jop.1995.66.7.579","article-title":"Immunohistochemical expression of extracellular matrix components of normal and healing periodontal tissues in the beagle dog","volume":"66","author":"Matsuura","year":"1995","journal-title":"J. Periodontol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1006\/jsbi.1999.4137","article-title":"Content and distribution of noncollagenous matrix proteins in bone and cementum: Relationship to speed of formation and collagen packing density","volume":"126","author":"Nanci","year":"1999","journal-title":"J. Struct Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1111\/jcpe.12055","article-title":"Events of wound healing\/regeneration in the canine supraalveolar periodontal defect model","volume":"40","author":"Dickinson","year":"2013","journal-title":"J. Clin. Periodontol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1600-0722.1998.tb02197.x","article-title":"Isolation of murine cementoblasts: Unique cells or uniquely-positioned osteoblasts?","volume":"106","author":"MacNeil","year":"1998","journal-title":"Eur. J. Oral Sci"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/03008209509016974","article-title":"Role of two mineral-associated adhesion molecules, osteopontin and bone sialoprotein, during cementogenesis","volume":"33","author":"MacNeil","year":"1995","journal-title":"Connect. Tissue Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1902\/jop.2006.060087","article-title":"Immunohistochemical study of bone sialoprotein and osteopontin in healthy and diseased root surfaces","volume":"77","author":"Lao","year":"2006","journal-title":"J. Periodontol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00441-005-1106-8","article-title":"Sequence of protein expression of bone sialoprotein and osteopontin at the developing interface between repair cementum and dentin in human deciduous teeth","volume":"320","author":"Bosshardt","year":"2005","journal-title":"Cell Tissue Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1034\/j.1600-0765.2000.035003115.x","article-title":"An immunohistochemical study of matrix molecules associated with barrier membrane-mediated periodontal wound healing","volume":"35","author":"Ivanovski","year":"2000","journal-title":"J. Periodontal Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1177\/10454411000110030101","article-title":"Osteopontin","volume":"11","author":"Sodek","year":"2000","journal-title":"Crit. Rev. Oral Biol. Med. Off. Publ. Am. Assoc. Oral Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/(SICI)1097-4644(1998)72:30\/31+<92::AID-JCB13>3.0.CO;2-A","article-title":"Osteopontin expression and function: Role in bone remodeling","volume":"72","author":"Denhardt","year":"1998","journal-title":"J. Cell Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000020591","article-title":"Osteopontin function in pathology: Lessons from osteopontin-deficient mice","volume":"7","author":"Rittling","year":"1999","journal-title":"Exp. Nephrol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e919159","DOI":"10.12659\/MSM.919159","article-title":"Osteopontin in Bone Metabolism and Bone Diseases","volume":"26","author":"Si","year":"2020","journal-title":"Med. Sci. Monit"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/jre.12794","article-title":"Identification of regulatory mRNA and microRNA for differentiation into cementoblasts and periodontal ligament cells","volume":"56","author":"Iwata","year":"2021","journal-title":"J. Periodontal Res."},{"key":"ref_61","unstructured":"(1992). ADA and AAP introduce dentists to new time saving periodontal evaluation system. Va. Dent. J., 69, 16\u201317."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1902\/jop.2008.070624","article-title":"Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice","volume":"79","author":"Rios","year":"2008","journal-title":"J. Periodontol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.biomaterials.2011.09.057","article-title":"Tissue engineering bone-ligament complexes using fiber-guiding scaffolds","volume":"33","author":"Park","year":"2012","journal-title":"Biomaterials"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/jcb.21224","article-title":"Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues","volume":"101","author":"Norris","year":"2007","journal-title":"J. Cell Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1600-0757.2005.00141.x","article-title":"Structure of periodontal tissues in health and disease","volume":"40","author":"Nanci","year":"2006","journal-title":"Periodontol. 2000"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1469-7580.2008.00856.x","article-title":"Regional structural characteristics of bovine periodontal ligament samples and their suitability for biomechanical tests","volume":"212","author":"Bosshardt","year":"2008","journal-title":"J. Anat."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/ejo\/8.3.167","article-title":"Blood supply in bone and periodontal ligament tissue surrounding mandibular fourth premolars in dogs\u2014A morphological study","volume":"8","author":"Follin","year":"1986","journal-title":"Eur. J. Orthod"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0003-9969(99)00030-8","article-title":"Blood volume in human bicuspid periodontal ligament determined by electron microscopy","volume":"44","author":"Foong","year":"1999","journal-title":"Arch. Oral Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1016\/j.biomaterials.2012.12.047","article-title":"Three-dimensional modeling of angiogenesis in porous biomaterial scaffolds","volume":"34","author":"Mehdizadeh","year":"2013","journal-title":"Biomaterials"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/ejo\/12.1.77","article-title":"An update on the biochemistry of the periodontal ligament","volume":"12","author":"Embery","year":"1990","journal-title":"Eur. J. Orthod"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/j.1600-0765.1982.tb01187.x","article-title":"Cell turnover in the periodontal ligament determined by continuous infusion of H3-thymidine using osmotic minipumps","volume":"17","author":"Gould","year":"1982","journal-title":"J. Periodontal Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/(SICI)1097-0185(199606)245:2<327::AID-AR15>3.0.CO;2-R","article-title":"Periodontal ligament cell population: The central role of fibroblasts in creating a unique tissue","volume":"245","author":"Lekic","year":"1996","journal-title":"Anat. Rec."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1600-0757.1997.tb00094.x","article-title":"The periodontal ligament: A unique, multifunctional connective tissue","volume":"13","author":"Beertsen","year":"1997","journal-title":"Periodontol. 2000"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Liu, J., Ruan, J., Weir, M.D., Ren, K., Schneider, A., Wang, P., Oates, T.W., Chang, X., and Xu, H.H.K. (2019). Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells. Cells, 8.","DOI":"10.3390\/cells8060537"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1111\/jcmm.13286","article-title":"Administration of signalling molecules dictates stem cell homing for in situ regeneration","volume":"21","author":"Li","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1600-051X.1985.tb01353.x","article-title":"New attachment formation on teeth with a reduced but healthy periodontal ligament","volume":"12","author":"Karring","year":"1985","journal-title":"J. Clin. Periodontol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.1600-051X.1980.tb01952.x","article-title":"Healing following implantation of periodontitis affected roots into bone tissue","volume":"7","author":"Karring","year":"1980","journal-title":"J. Clin. Periodontol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1600-0757.2006.00157.x","article-title":"Biology and principles of periodontal wound healing\/regeneration","volume":"41","author":"Polimeni","year":"2006","journal-title":"Periodontol. 2000"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1600-0757.2011.00432.x","article-title":"Advanced reconstructive technologies for periodontal tissue repair","volume":"59","author":"Ramseier","year":"2012","journal-title":"Periodontol. 2000"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/sctm.18-0181","article-title":"Concise Review: Periodontal Tissue Regeneration Using Stem Cells: Strategies and Translational Considerations","volume":"8","author":"Xu","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_81","first-page":"e303","article-title":"Engineered scaffolds and cell-based therapy for periodontal regeneration","volume":"15","author":"Carmagnola","year":"2017","journal-title":"J. Appl. Biomater. Funct Mater."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"d\u2019vanzo, N., Bruno, M.C., Giudice, A., Mancuso, A., Gaetano, F., Cristiano, M.C., Paolino, D., and Fresta, M. (2021). Influence of Materials Properties on Bio-Physical Features and Effectiveness of 3D-Scaffolds for Periodontal Regeneration. Molecules, 26.","DOI":"10.3390\/molecules26061643"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s10856-018-6175-9","article-title":"Optimising collagen scaffold architecture for enhanced periodontal ligament fibroblast migration","volume":"29","author":"Ashworth","year":"2018","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/jbm.a.32834","article-title":"Design of three-dimensional biomimetic scaffolds","volume":"94","author":"Owen","year":"2010","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1016\/j.biomaterials.2010.12.019","article-title":"Controlled architectural and chemotactic studies of 3D cell migration","volume":"32","author":"Tayalia","year":"2011","journal-title":"Biomaterials"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/prd.12155","article-title":"Description of the periodontal pocket in preclinical models: Limitations and considerations","volume":"76","author":"Donos","year":"2018","journal-title":"Periodontol. 2000"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1902\/jop.1994.65.12.1169","article-title":"Discussion: Animal models in reconstructive therapy","volume":"65","author":"Selvig","year":"1994","journal-title":"J. Periodontol"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1600-051X.2010.01544.x","article-title":"Periodontal wound healing\/regeneration following implantation of recombinant human growth\/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs","volume":"37","author":"Lee","year":"2010","journal-title":"J. Clin. Periodontol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1600-051X.2012.01868.x","article-title":"Maturation of alveolar bone following implantation of an rhGDF-5\/PLGA composite into 1-wall intra-bony defects in dogs: 24-week histometric observations","volume":"39","author":"Park","year":"2012","journal-title":"J. Clin. Periodontol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/prd.12052","article-title":"Animal models for periodontal regeneration and peri-implant responses","volume":"68","author":"Kantarci","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_91","first-page":"754857","article-title":"Animal models for periodontal disease","volume":"2011","author":"Oz","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/jcbfm.2010.220","article-title":"Animal research: Reporting in vivo experiments--the ARRIVE guidelines","volume":"31","author":"Kilkenny","year":"2011","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1111\/jcpe.13426","article-title":"Preclinical evaluation of the effect of a volume-stable collagen matrix on periodontal regeneration in two-wall intrabony defects","volume":"48","author":"Imber","year":"2021","journal-title":"J. Clin. Periodontol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1006\/bbrc.1998.0117","article-title":"Activation of stress-activated protein kinases by hepatocyte isolation induces gene 33 expression","volume":"254","author":"Varley","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1034\/j.1600-9657.2002.00087.x","article-title":"PCNA-expression of cementoblasts and fibroblasts on the root surface after extraoral rinsing for decontamination","volume":"18","author":"Ebensberger","year":"2002","journal-title":"Dent. Traumatol"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1902\/jop.2000.71.10.1567","article-title":"The effect of age on proliferating cell nuclear antigen expression in oral gingival epithelium of healthy and inflamed human gingiva","volume":"71","author":"Ayhan","year":"2000","journal-title":"J. Periodontol"},{"key":"ref_97","first-page":"473","article-title":"Proliferating cell nuclear antigen immunoreactivity and prognosis of gastrointestinal stromal tumors","volume":"8","author":"Franquemont","year":"1995","journal-title":"Mod. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1380851","DOI":"10.1155\/2017\/1380851","article-title":"Periodontal Ligament Stem Cells in the Periodontitis Microenvironment Are Sensitive to Static Mechanical Strain","volume":"2017","author":"Liu","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/BF01047461","article-title":"The assessment of cellular proliferation by immunohistochemistry: A review of currently available methods and their applications","volume":"24","author":"Yu","year":"1992","journal-title":"Histochem. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/10915\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:11:06Z","timestamp":1760166666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/10915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,9]]},"references-count":99,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms222010915"],"URL":"https:\/\/doi.org\/10.3390\/ijms222010915","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,9]]}}}